Folate-conjugated chitosan–polylactide nanoparticles for enhanced intracellular uptake of anticancer drug

Chitosan was conjugated with folic acid (FA) and the resulting chitosan derivatives with a FA-substitution degree of around 6 % was used to synthesize FA-conjugated chitosan–polylactide (FA–CH–PLA) copolymers to build a drug carrier with active targeting characteristics for the anticancer drug of paclitaxel (PTX). Selected FA–CH–PLAs with various polylactide percentages of about 40 wt% or lower were employed to fabricate nanoparticles using sodium tripolyphosphate as a crosslinker, and different types of nanoparticles were endued with similar average particle-sizes located in a range between 100 and 200 nm. Certain types of PTX-loaded FA–CH–PLA nanoparticles having encapsulation efficiency of around 90 % and initial load of about 12 % were able to release PTX in a controlled manner with significant regulation by polylactide content in FA–CH–PLAs. Targeting characteristic of achieved nanoparticles was confirmed using FA-receptor-expressed MCF-7 breast cancer cells. The uptake of PTX revealed that optimized FA–CH–PLA nanoparticles with an equivalent PTX-dose of around 1 μg/mL could have more than sixfold increasing abilities to facilitate intracellular paclitaxel accumulation in MCF-7 cells after 24 h treatment as compared to free PTX. At a relatively safe equivalent PTX-dose for normal MCF-10A mammary epithelial cells, the obtained results from Hoechst 33342 staining indicated that optimized PTX-loaded FA–CH–PLA nanoparticles had more than threefold increasing abilities to induce MCF-7 cell apoptosis in comparison to free PTX.